According to the Ministry of Health and Welfare, oral cancer mortality ranked fifth in cancer deaths in Taiwan in 2012. Most oral cancers are diagnosed at mid-to-late stage, resulting in high recurrence and mortality. Therefore, it is important to identify individuals at high risk for developing oral cancer, particularly patients with oral potentially malignant disorder (OPMD), and establish a more intense clinical care and followup program for these individuals. This will lead to a reduction in the incidence and mortality of oral cancer. The current study investigated the association between lifestyle factors and risk of OPMD. Our analysis included data collected by interview survey of 129 cases and 49 controls. After adjusting for age and education, our results showed that betel quid chewing and cigarette smoking were associated with an increased risk of OPMD. In contrast, using dental floss regularly and consumption of eggs and citrus fruits more than twice a week were inversely associated with OPMD risk. Overall, our results identified several lifestyle factors that were associated with an increased or decreased risk of OPMD.